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1.
Medicine (Baltimore) ; 98(52): e18449, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876727

RESUMO

Twist and E-cadherin are crucial for the development of different types of cancer; however, their clinical significance in adenocarcinoma of the gastroesophageal junction (AGE) remains unknown. Here, we investigated the correlation between the expression of Twist and E-cadherin and their impact on the clinical outcomes and prognosis of patients with AGE and proximal gastric carcinoma (PGC).Using immunohistochemistry, we determined the expression of Twist and E-cadherin in the tissue samples of patients with AGE and PGC. The correlation of the expression of Twist and E-cadherin with the clinicopathological factors was assessed by using the chi-square test, Fisher exact test, and non-parametric Mann-Whitney U test. The Kaplan-Meier method along with the log-rank test and Cox proportional-hazards model were used to evaluate the correlation of Twist and E-cadherin expression with the overall survival (OS) of patients.Overall, 94 patients with AGE (n = 45, 47.87%) or PGC (n = 49, 52.13%) who underwent primary tumor resection were included in this study. The median follow-up period was 40.5 months. We observed a significant difference in the smoking status (P < .001) and differentiation grade (P = .004) between patients with AGE and PGC. There was a significant association of a high Twist expression with T stage (only in PGC, P = .008), lymph node metastasis (AGE, P = .075; PGC, P = .051), and advanced pathological stages (AGE, P = .019; PGC, P = .006). A low E-cadherin expression showed similar results; however, it was not significantly associated with the advanced pathological stages of AGE (P = .372). A low E-cadherin expression was significantly associated with a low differentiation grade of AGE (P = .002). In addition, a significant inverse relationship was observed between Twist and E-cadherin expression. The Kaplan-Meier survival analysis and Cox regression analysis revealed that a high Twist expression and low E-cadherin expression were independent prognostic factors for short OS of patients with AGE or PGC.A high Twist expression or low E-cadherin expression was associated with unfavorable clinicopathological factors and independently predicted short OS of patients with AGE or PGC.


Assuntos
Adenocarcinoma/metabolismo , Caderinas/metabolismo , Carcinoma/metabolismo , Junção Esofagogástrica/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Caderinas/análise , Carcinoma/química , Carcinoma/diagnóstico , Junção Esofagogástrica/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/química , Prognóstico , Neoplasias Gástricas/química , Neoplasias Gástricas/diagnóstico , Proteína 1 Relacionada a Twist/química
2.
Medicine (Baltimore) ; 98(47): e18122, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764853

RESUMO

MicroRNAs (miRNAs) are endogenous, non-coding class of RNAs with functions in the regulation of genes expressions. Dysregulated expressions of miRNAs play important roles in carcinogenesis and cancer progression by targeting various oncogenes and tumor-suppressor genes. miRNAs represent a new field for molecular diagnosis and prognosis of colorectal cancer (CRC) due to their high tissue specificity, their stability, and their dysregulated expression in tumor development.This study aimed to investigate using the qRT-PCR method the expression profile and prognostic value of 11 mature miRNAs in a cohort of 82 Romanian patients diagnosed with CRC. The relationship between the expression levels of selected miRNAs and clinicopathologic features were evaluated using ANOVA and Pearson test. In addition, the receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic values of the miRNAs to discriminate cancerous from non-cancerous states of the samples.The expression levels of miR-30c, miR-144, miR-375, miR-214, and miR-195 in CRC tissue were significantly downregulated (all P < .05; Paired T-Test) than that in normal adjacent tissue sample (NATS), while the expression of miR-141, miR-182, miR-183, miR-21, and miR-370 in CRC tissue were significantly upregulated (all P < .001) than that in NATS. Moreover, the expression levels of miR-182, miR-183, miR-141, and miR-21 were demonstrated to be associated with a gradual increase in fold change expression with depth of tumor invasion (all P < .05), lymph node invasion (all P < .001), and maximal increase with distant metastasis (all P < .001). Moreover, the analysis of ROC curves revealed that AUC (95% CI) of miR-182, miR-183, miR-141, and miR-21 in diagnosis of CRC was 0.76 (0.66-0.87), 0.85 (0.78-0.94), 0.77 (0.62-0.92), 0.83 (0.73-0.90), respectively. The univariate and multivariate Cox-proportional hazard regression for all variables revealed that the nodal status, distant metastasis, miR-21, miR-141, miR-182, and miR-183 were independent prognostic markers of CRC.In conclusion, altered expressions of miR-21, miR-141, miR-182, and miR-183 in CRC varies at different stages of CRC development and may serve as potential diagnosis molecular biomarkers in Romanian patients with CRC. Further investigations are needed to confirm our findings.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/química , Neoplasias Colorretais/diagnóstico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Romênia
3.
Anticancer Res ; 39(11): 6403-6412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704874

RESUMO

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.


Assuntos
Fator Estimulador de Colônias de Macrófagos/análise , Metaloproteases/análise , Inibidores Teciduais de Metaloproteinases/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteases/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Displasia do Colo do Útero/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
4.
Curr Gastroenterol Rep ; 21(9): 42, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346777

RESUMO

PURPOSE OF REVIEW: There has been an exponential increase in the incidence of esophageal adenocarcinoma (EAC) over the last half century. Barrett's esophagus (BE) is the only known precursor lesion of EAC. Screening for BE in high-risk populations has been advocated with the aim of identifying BE, followed by endoscopic surveillance to detect dysplasia and early stage cancer, with the intent that treatment can improve outcomes. We aimed to review BE screening methodologies currently recommended and in development. RECENT FINDINGS: Unsedated transnasal endoscopy allows for visualization of the distal esophagus, with potential for biopsy acquisition, and can be done in the office setting. Non-endoscopic screening methods being developed couple the use of swallowable esophageal cell sampling devices with BE specific biomarkers, as well as trefoil factor 3, methylated DNA markers, and microRNAs. This approach has promising accuracy. Circulating and exhaled volatile organic compounds and the foregut microbiome are also being explored as means of detecting EAC and BE in a non-invasive manner. Non-invasive diagnostic techniques have shown promise in the detection of BE and may be effective methods of screening high-risk patients.


Assuntos
Adenocarcinoma/diagnóstico , Esôfago de Barrett/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/diagnóstico , Esôfago/patologia , Lesões Pré-Cancerosas/diagnóstico , Adenocarcinoma/química , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Esôfago de Barrett/complicações , Esôfago de Barrett/genética , Esôfago de Barrett/microbiologia , Biomarcadores Tumorais/análise , Endoscopia por Cápsula , Neoplasias Esofágicas/química , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/microbiologia , Esofagoscopia , Esôfago/química , Esôfago/microbiologia , Humanos , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/microbiologia
5.
J Clin Pathol ; 72(11): 762-770, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256008

RESUMO

AIMS: Knowledge regarding the genetic features of ampullary carcinoma (AC) in European patients is limited. The utility of tumour markers for the establishment of a malignant diagnosis in biopsies from the ampullary region has not been fully elucidated. We aimed to describe the clinical, pathological, immunohistochemical (IHC) and genetic features of a Danish series of surgically resected ACs. METHODS: Surgically resected ACs (n=59) were examined regarding (1) clinicopathological features, (2) histological subtypes, (3) expression of IMP3, maspin, MUC5AC and S100P and (4) next-generation sequencing using a hybrid capture-based platform (Illumina HiSeq2500), including 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. Tumour mutational burden (TMB) and microsatellite instability (MSI) were also evaluated. RESULTS: Pancreatobiliary adenocarcinomas (PB-AC), intestinal adenocarcinomas (INT-AC), other ampullary tumours and mixed adenocarcinomas represented 45.8%, 23.7%, 16.9% and 13.6%. The proportion of IHC-positive ACs (score ≥2) was: Maspin (94.9%), IMP3 (67.8%), S100P (39.0%) and MUC5AC (18.6%). Most frequently altered genes were TP53 (59.3%), KRAS (40.7%), APC (27.8%), SMAD4 (20.4%), CDKN2A (16.7%) and ARID2/PIK3CA (each 11.1%). MUC5AC and S100P were frequently expressed in PB-AC, APC alterations frequent in INT-AC, SOX9 alterations were exclusive in INT-AC and MDM2 and FRS2 alterations in PB-AC. Four of 49 ACs (8.2%) were TMB-high/MSI-high and showed loss of MLH1 and PMS2. CONCLUSIONS: PB-AC was the most frequent histological subtype of AC. Maspin and IMP3 were the IHC tumour markers with the highest sensitivity. Adenocarcinoma subtypes differed regarding several genetic alterations, whose predictive value remains to be evaluated.


Assuntos
Adenocarcinoma/química , Adenocarcinoma/genética , Ampola Hepatopancreática/química , Biomarcadores Tumorais , Neoplasias do Sistema Digestório/química , Neoplasias do Sistema Digestório/genética , Perfilação da Expressão Gênica , Imuno-Histoquímica , Mutação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação ao Cálcio/genética , Dinamarca , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/cirurgia , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mucina-5AC/análise , Mucina-5AC/genética , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Fenótipo , Valor Preditivo dos Testes , Sistema de Registros , Ribonucleoproteínas Nucleolares Pequenas/análise , Ribonucleoproteínas Nucleolares Pequenas/genética , Serpinas/análise , Serpinas/genética
6.
J Pak Med Assoc ; 69(6): 788-793, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31189283

RESUMO

OBJECTIVE: To investigate the frequency of Human Epidermal Growth Factor Receptor 2 over expression in gastric adenocarcinoma by immunohistochemistry and to find the association of its expression with clinicopathological parameters. . METHODS: The descriptive cross-sectional study was conducted at Rehman Medical Institute, Peshawar, Pakistan, from January to December 2016, and comprised consecutive formalin-fixed and paraffin-embedded samples of gastric adenocarcinoma. The cases were scored for Human Epidermal Growth Factor Receptor 2 expression according to criteria cited in Trastuzumab for Gastric Cancer trial. Correlation of the expression with different clinicopathological parameters was determined. SPSS 23 was used for data analysis. RESULTS: Of the 55 cases, 49(89%) were biopsies and 6(11%) were gastrectomies. Among the patients whose samples were tested, 41(74.5%) were male. The overall mean age was 59.16}12.58 years (range: 38-95 years). Human Epidermal Growth Factor Receptor 2 overexpression (3+) was present in 19(34.5%) cases.Out of 21(38.2%) cases of moderately differentiated adenocarcinoma, 10(47.6%) showed overexpression. It was commonest in tumours of the fundus area 7(31.6%). No association of the expression was found with tumour's histological grade and location, or with patient's gender and age (p>0.05 each).. CONCLUSIONS: More than one-third of the sample had overexpression of Human Epidermal Growth Factor Receptor 2.


Assuntos
Adenocarcinoma , Receptor ErbB-2/análise , Neoplasias Gástricas , Adenocarcinoma/química , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/química , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia
7.
Anticancer Res ; 39(6): 3231-3240, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177173

RESUMO

BACKGROUND/AIM: To determine the prognostic effects of immunohistochemical biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma of the uterine cervix. MATERIALS AND METHODS: This study included 42 patients receiving definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 13, 21, and 8 patients were classified as having stage IB2, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including those for hypoxia, cell proliferation, cell adhesion, immunogenicity, and evasion of apoptosis, were analyzed using tissue microarrays from biopsy specimens. RESULTS: Myeloid cell leukemia-1 (MCL1) overexpression and the presence of pelvic lymph node metastasis were two prognostic factors for inferior cancer-specific survival. A higher H-score for c-MYC proto-oncogene, bHLH transcription factor (c-MYC) was associated with lower pelvic relapse-free survival. CONCLUSION: For patients with adenocarcinoma of the uterine cervix requiring definitive CRT, treatment outcomes can be stratified by the immunohistochemical biomarkers MCL1 and c-MYC for cancer death and local failure, respectively.


Assuntos
Adenocarcinoma/terapia , Biomarcadores Tumorais/análise , Quimiorradioterapia , Imuno-Histoquímica , Proteína de Sequência 1 de Leucemia de Células Mieloides/análise , Proteínas Proto-Oncogênicas c-myc/análise , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Análise Serial de Tecidos , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
8.
Virchows Arch ; 475(1): 59-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31177317

RESUMO

Sarcomatoid carcinomas recently came into the spotlight through genetic profiling studies and also as a distinct model of epithelial-mesenchymal transition. The literature on sarcomatoid carcinomas of gallbladder is limited. In this study, 656 gallbladder carcinomas (GBC) were reviewed. Eleven (1.7%) with a sarcomatoid component were identified and analyzed in comparison with ordinary GBC (O-GBC). Patients included 9 females and 2 males (F/M = 4.5 vs. 3.9) with a mean age-at-diagnosis of 71 (vs. 64). The median tumor size was 4.6 cm (vs. 2.5; P = 0.01). Nine patients (84%) presented with advanced stage (pT3/4) tumor (vs. 48%). An adenocarcinoma component constituting 1-75% of the tumor was present in nine, and eight had surface dysplasia/CIS; either in situ or invasive carcinoma was present in all cases. An intracholecystic papillary-tubular neoplasm was identified in one. Seven showed pleomorphic-sarcomatoid pattern, and four showed subtle/bland elongated spindle cells. Three had an angiosarcomatoid pattern. Two had heterologous elements. One showed few osteoclast-like giant cells, only adjacent to osteoid. Immunohistochemically, vimentin, was positive in six of six; P53 expression was > 60% in six of six, keratins in six of seven, and p63 in two of six. Actin, desmin, and S100 were negative. The median Ki67 index was 40%. In the follow-up, one died peri-operatively, eight died of disease within 3 to 8 months (vs. 26 months median survival for O-GBC), and two were alive at 9 and 15 months. The behavior overall was worse than ordinary adenocarcinomas in general but was not different when grade and stage were matched. In summary, sarcomatoid component is identified in < 2% of GBC. Unlike sarcomatoid carcinomas in the remainder of pancreatobiliary tract, these are seldom of the "osteoclastic" type and patients present with large/advanced stage tumors. Limited data suggests that these tumors are aggressive with rapid mortality unlike pancreatic osteoclastic ones which often have indolent behavior.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Carcinoma in Situ/patologia , Neoplasias da Vesícula Biliar/patologia , Neoplasias Complexas Mistas/patologia , Sarcoma/patologia , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Carcinoma in Situ/química , Carcinoma in Situ/mortalidade , Carcinoma in Situ/cirurgia , Feminino , Neoplasias da Vesícula Biliar/química , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/mortalidade , Neoplasias Complexas Mistas/cirurgia , Sarcoma/química , Sarcoma/mortalidade , Sarcoma/cirurgia , Fatores de Tempo , Resultado do Tratamento
9.
Clin Transl Oncol ; 21(10): 1432-1439, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31025168

RESUMO

INTRODUCTION: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3-0.9% of the appendectomies, 35-58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The most frequent clinical presentation is abdominal pain associated with a picture of acute appendicitis. MATERIALS AND METHODS: We present 3 clinical cases of appendix GCC, 2 subjected to cytoreductory surgery plus intraperitoneal hyperthermic chemotherapy and a third, who is currently receiving neoadjuvant treatment with a good response to chemotherapy and who will be offered the same treatment as the first two patients. Given the unpredictable behavior of these tumors, the use of molecular markers could help us to predict their behavior and prognosis. In this context, the TP73 gene would make an interesting putative marker. ∆Np73 has been described as overexpressed in a great variety of tumor types including colon cancer and this up-regulation is associated with a poor prognosis. To evidence its role in this malignancy, we evaluate here the status of ∆Np73 in the primary tumor and normal counterpart tissues, in the metastatic implants and in healthy areas of the peritoneum from the appendicular GCC patients. In addition, we checked the expression levels of this p73 variant in the tumor and normal tissue of 26 patients with colon cancer. RESULTS: Remarkably, 2 patients showed significant ∆Np73 down-regulation in both the primary tumor and the implants. Case 1 presented a fourfold decrease of levels in the primary tumor and 20-fold decrease in the implants. Case 2 showed a seven- and fourfold down-regulation in the primary tumor and implants, respectively. However, Case 3 showed an up-regulation of 53- and threefold in the primary tumor and implants, respectively. CONCLUSION: Goblet cell carcinoma of the appendix is very rate. It tends to seed throughout the peritoneum, making aggressive surgical cytoreduction and chemotherapy viable treatment options. Investigation into the molecular basis of these tumors may improve the diagnosis, prognosis and therapeutic decisions regarding these patients. ∆Np73 seems a good candidate for further analysis in longer series.


Assuntos
Adenocarcinoma/química , Neoplasias do Apêndice/química , Biomarcadores Tumorais/análise , Células Caliciformes/química , Neoplasias Ovarianas/química , Neoplasias Peritoneais/química , Proteína Tumoral p73/análise , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Colo/química , Neoplasias do Colo/química , Procedimentos Cirúrgicos de Citorredução , Regulação para Baixo , Feminino , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Peritônio/química
10.
Prostate ; 79(7): 701-708, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30865311

RESUMO

BACKGROUND: Plasma-based cell-free DNA is an attractive biospecimen for assessing somatic mutations due to minimally-invasive real-time sampling. However, next generation sequencing (NGS) of cell-free DNA (cfDNA) may not be appropriate for all patients with advanced prostate cancer (PC). METHODS: Blood was obtained from advanced PC patients for plasma-based sequencing. UW-OncoPlex, a ∼2 Mb multi-gene NGS panel performed in the CLIA/CAP environment, was optimized for detecting cfDNA mutations. Tumor tissue and germline samples were sequenced for comparative analyses. Multivariate logistic regression was performed to determine the clinical characteristic associated with the successful detection of somatic cfDNA alterations (ie detection of at least one clearly somatic PC mutation). RESULTS: Plasma for cfDNA sequencing was obtained from 93 PC patients along with tumor tissue (N = 67) and germline (N = 93) controls. We included data from 76 patients (72 prostate adenocarcinoma; 4 variant histology PC) in the analysis. Somatic DNA aberrations were detected in 34 cfDNA samples from patients with prostate adenocarcinoma. High PSA level, high tumor volume, and castration-resistance were significantly associated with successful detection of somatic cfDNA alterations. Among samples with somatic mutations detected, the cfDNA assay detected 93/102 (91%) alterations found in tumor tissue, yielding a clustering-corrected sensitivity of 92% (95% confidence interval 88-97%). All germline pathogenic variants present in lymphocyte DNA were also detected in cfDNA (N = 12). Somatic mutations from cfDNA were detected in 30/33 (93%) instances when PSA was >10 ng/mL. CONCLUSIONS: Disease burden, including a PSA >10 ng/mL, is strongly associated with detecting somatic mutations from cfDNA specimens.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/química , Biomarcadores Tumorais/análise , DNA Tumoral Circulante/análise , Neoplasias da Próstata/sangue , Neoplasias da Próstata/química , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Efeitos Psicossociais da Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
11.
Adv Anat Pathol ; 26(2): 75-83, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30601149

RESUMO

Goblet cell carcinoid (GCC) or goblet cell carcinoma is a unique mixed endocrine-exocrine neoplasm that is almost exclusively seen in the appendix. The hallmark of GCC is the concentric infiltration of the appendiceal wall by small tight clusters, nests or cords of tumor cells that exhibit a goblet cell morphology with a small compressed nucleus and conspicuous intracytoplasmic mucin. The coexistence of high-grade adenocarcinoma with GCC has been increasingly recognized as a common finding, which has been called adenocarcinoma ex GCC or mixed GCC-adenocarcinoma. A number of studies have shown that it is the high-grade adenocarcinomatous component that dictates the prognosis. Several histologic classification/grading systems have been proposed, which correlate with overall patient survival. Treatment options are primarily based on tumor stage and the presence or absence of a high-grade adenocarcinomatous component.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Apêndice/patologia , Tumor Carcinoide/patologia , Células Caliciformes/patologia , Neoplasias Complexas Mistas/patologia , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Neoplasias do Apêndice/química , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/terapia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Tumor Carcinoide/química , Tumor Carcinoide/mortalidade , Tumor Carcinoide/terapia , Células Caliciformes/química , Humanos , Imuno-Histoquímica , Técnicas de Diagnóstico Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/mortalidade , Neoplasias Complexas Mistas/terapia , Resultado do Tratamento
12.
Zhonghua Bing Li Xue Za Zhi ; 48(2): 92-97, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30695858

RESUMO

Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.


Assuntos
Adenocarcinoma/química , Ampola Hepatopancreática/química , Biomarcadores Tumorais/análise , Neoplasias do Ducto Colédoco/química , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Fator de Transcrição CDX2/análise , Neoplasias do Ducto Colédoco/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratina-17/análise , Queratina-20/análise , Queratina-7/análise , Masculino , Pessoa de Meia-Idade , Mucina-1/análise , Mucina-2/análise
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 211: 356-362, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30593945

RESUMO

Techniques to inspect and analyze human colorectal cancer cell lines by using terahertz time-domain attenuated total reflection spectroscopy (THz TD-ATR) were investigated. The characteristics of THz absorption spectra of two colorectal cancer cell lines DLD-1 and HT-29 in aqueous solutions with different concentrations were studied. Different spectral features were observed compared to normal cell line. Identification results based on different parameters including absorption coefficient, refractive index, real and imaginary parts of complex permittivity, dielectric loss tangent were discussed. This research may be promising for quick and instant inspection of liquid samples by using THz time-domain spectroscopy in medical applications.


Assuntos
Adenocarcinoma/química , Neoplasias do Colo/química , Espectroscopia Terahertz/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Células HT29 , Humanos , Camundongos , Células NIH 3T3
15.
Exp Mol Pathol ; 106: 17-26, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30439350

RESUMO

Invadopodia, cancer cell protrusions with proteolytic activity, are functionally associated with active remodeling of the extracellular matrix. Here, we show that the invadopodia-related protein TKS5 is expressed in human pancreatic adenocarcinoma lines, and demonstrate that pancreatic cancer cells depend on TKS5 for invadopodia formation and function. Immunofluorescence staining of human pancreatic cancer cells reveals that TKS5 is a marker of mature and immature invadopodia. We also analyze the co-staining patterns of TKS5 and the commonly used invadopodia marker Cortactin, and find only partial co-localization of these two proteins at invadopodia, with a large fraction of TKS5-positive invadopodia lacking detectable levels of Cortactin. Whereas compelling evidence exist on the role of invadopodia as mediators of invasive migration in cultured cells and in animal models of cancer, these structures have never been detected inside human tumors. Here, using antibodies against TKS5 and Cortactin, we describe for the first time structures strongly resembling invadopodia in various paraffin-embedded human tumor surgical specimens from pancreas and other organs. Our results strongly suggest that invadopodia are present inside human tumors, and warrants further investigation on their regulation and occurrence in surgical specimens, and on the value of TKS5 antibodies as pathological research and diagnostic tools.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Adenocarcinoma/patologia , Proteínas de Neoplasias/fisiologia , Neoplasias Pancreáticas/patologia , Podossomos/fisiologia , Adenocarcinoma/química , Adenocarcinoma/cirurgia , Adenocarcinoma/ultraestrutura , Adulto , Idoso , Linhagem Celular Tumoral , Cortactina/análise , Feminino , Técnica Direta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias/química , Neoplasias/patologia , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/ultraestrutura , Inclusão em Parafina , Podossomos/química , Podossomos/ultraestrutura , Interferência de RNA , RNA Interferente Pequeno/genética
16.
Virchows Arch ; 474(1): 79-86, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30324235

RESUMO

Gastric-type adenocarcinoma (GA) is an aggressive subtype of cancer of the uterine cervix. Several immunohistochemical markers for gastric mucins, such as mucin 6 (MUC6) and N-acetylglucosamine α1 → 4galactose → R (αGlcNAc-R), which is recognized by HIK1083 antibody, have been introduced for diagnosis of GA and lobular endocervical glandular hyperplasia (LEGH). However, MUC6 is also expressed in normal endocervical glands and HIK1083 antibody has limited availability. Trefoil factor family 2 protein (TFF2) is secreted by gastric, but not normal endocervical glands. Here, we evaluated TFF2 immunostaining for detection of a gastric immunophenotype in endocervical glandular lesions. We compared TFF2, αGlcNAc-R, and MUC6 expression in 103 endocervical glandular lesions: LEGH (n = 23), adenocarcinoma in situ/microinvasive adenocarcinoma (AIS-MIA) (n = 29), and invasive adenocarcinoma (usual type [UA], n = 26; GA, n = 11; intestinal type [IA], n = 2; signet ring cell type [Sig], n = 2; and mucinous adenocarcinoma not otherwise specified [NOS], n = 10). TFF2 and αGlcNAc-R expression was completely concordant in each subtype: LEGH (100%), AIS-MIA (44.8%), UA (26.9%), GA (90.9%), IA (100%), Sig (0%), and NOS (20%). TFF2 staining scores were significantly correlated with those of αGlcNAc-R in these lesions. TFF2 and αGlcNAc-R immunoreactivity was present in cytoplasmic mucins and luminal secretions. TFF2 and αGlcNAc-R were not expressed in the normal endocervical glands. MUC6 was frequently expressed in normal endocervical glands and endocervical glandular lesions. Endocervical adenocarcinomas sometimes stained only for MUC6. TFF2 is a promising immunohistochemical marker and its identification in uterine cervical secretion is a potentially useful diagnostic test for endocervical glandular lesions with gastric differentiation.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Hiperplasia Endometrial/metabolismo , Imuno-Histoquímica , Fator Trefoil-2/análise , Neoplasias do Colo do Útero/química , Acetilglucosamina/análise , Adenocarcinoma/patologia , Adulto , Idoso , Diferenciação Celular , Hiperplasia Endometrial/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mucina-6/análise , Fenótipo , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/patologia
17.
Dig Dis Sci ; 64(6): 1486-1492, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30560333

RESUMO

BACKGROUND: Huntingtin-associated protein 1 (HAP1) is a neuronal protein that is predominantly expressed in neurons in the brain. HAP1 is critical for maintenance of neuronal survival as well as regulation of food intake and body weight in animals. In addition to the criticalrole of HAP1 in the central nervous system, HAP1 is also found in endocrine cells, raising an interesting issue of whether HAP1 is expressed in the digestive system. AIMS: To examine the expression and localization of HAP1 in the human gastrointestinal tract and to compare the differences of the HAP1 expression between benign and malignant tissues in the digestive system. METHODS: We used Western blot and immunohistochemistry to examine the expression and distribution of HAP1 in the human gastrointestinal tract tissues. RESULTS: We observed that the presence of HAP1-positive cells in the gastrointestinal tract was not uniform with immunohistochemistry staining. Western blot revealed that only one isoform (75KD) HAP1 was present in the human gastrointestinal system. Interestingly, the expression of HAP1 was higher in the stomach than other regions of the gastrointestinal tract and was at the lowest level in the intestine. We also found that HAP1 was unlikely altered in benign gastric polyps, but was downregulated in pancreatic cancer. CONCLUSIONS: This is the first study showing the differential expression and location of HAP1 in the human digestive system. These findings suggested that HAP1 may have cell-type-dependent function in the gastrointestinal tract and may serve as a diagnostic marker for pancreatic cancer.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Trato Gastrointestinal/química , Proteínas do Tecido Nervoso/análise , Neoplasias Pancreáticas/química , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Regulação para Baixo , Feminino , Trato Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia
18.
Turk Patoloji Derg ; 35(3): 247-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28832082

RESUMO

We describe an unusual case of a Peutz-Jeghers syndrome associated with a composite synchronous cervical neoplasia comprising precursor "lobular endocervical glandular hyperplasia (LEGH)", "minimal deviation adenocarcinoma (MDA)" and "gastric-type adenocarcinoma (GTA)" along with a serous tubal intraepithelial lesion (STIL) in the right fallopian tube. A 24-year-old woman presented with a white mucoid discharge and bleeding per vaginum for one year. Histopathological evaluation showed MDA & GTA in FIGO grade III with pelvic lymph node metastasis despite a deceptively bland tumour morphology and low Ki-67 index, indicating an aggressive tumour course and poor prognosis. Diagnostic marker profile in the cervix showed gastric type mucin and positive expression of CK-7, CK-20 (patchy), CEA, and negative CDX-2, p16, ER and PR. Further an attempt at eliciting the oncogenesis pathway in view of the p16 and HPV negative nature of the gastric type cervical adenocarcinoma showed negativity for p53 but activation of cyclin D1. Growth factors including Her2 and EGFR were negative while VEGFR was over-expressed. She was treated by radical hysterectomy and pelvic radiation. She was free from recurrence at the 12-month follow-up. This is a first-time report of a STIL in the fallopian tube which was validated by a unilateral mutant type p53 expression and increased Ki67 index, associated with synchronous gastric type adenocarcinoma of the cervix in all stages of evolution.


Assuntos
Adenocarcinoma/patologia , Hiperplasia Endometrial/patologia , Neoplasias das Tubas Uterinas/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Primárias Múltiplas/patologia , Síndrome de Peutz-Jeghers/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/química , Adenocarcinoma/genética , Adenocarcinoma/terapia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/terapia , Neoplasias das Tubas Uterinas/química , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/terapia , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Imagem por Ressonância Magnética , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/química , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/terapia , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/terapia , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Adulto Jovem
19.
Bioelectrochemistry ; 125: 15-24, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30196014

RESUMO

Electroporation of cells is usually studied using cell suspensions or monolayer cultures. 3D scaffolds for cell culture have been recently designed in order to reproduce in vitro the complex and multifactorial environment experimented in vivo by cells. In fact, it is well known that 2D cell cultures are not able to simulate the complex interactions between the cells and their extracellular matrix (ECM). Recently, some examples of 3D models, like spheroids, have been investigated also in the electroporation field. Spheroids have been proposed in electrochemotherapy (ECT) studies to mimic tumor in vivo conditions: they are easy-to-handle 3D models but their sensitivity to electric field pulses depends from their diameter and, more interestingly, despite being relevant for intercellular junctions, they are not so much so for cell-ECM interactions. In this work, we propose a 3D macroscopic myxoid matrix for cell culture that would mimic the in vivo environment of myxoid stroma tumors. The myxoid stroma consists of abundant basic substances with large amounts of glycosaminoglycans (hyaluronic acid) and proteoglycans, poor collagen fibers and no elastin content. In the proposed approach, tumor cells seeded on 3D scaffolds mimic of myxoid stroma can establish both cell-cell and cell-ECM 3D interactions. The MCF7 cells (human breast adenocarcinoma cell line) were seeded in complete culture medium. Cell cultures were incubated at 37 °C for either 24 h, 3 days or 7 day. Some samples were used to assess cell vitality using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test and others for electroporation tests and for histopathological analysis. The electroporation has been verified by the fluorescent dye Propidium cellular uptake. The proposed myxoid stroma scaffold induces cell proliferation and shows fibrous structures produced by cells, the concentration of which increases with culture time. The proposed matrix will be used for further investigations as a new scaffold for cell culture. Tumor cells grown into these new scaffolds will be used to evaluate electroporation including the stroma effect.


Assuntos
Técnicas de Cultura de Células/métodos , Eletroporação/métodos , Tecidos Suporte/química , Microambiente Tumoral , Adenocarcinoma/química , Adenocarcinoma/patologia , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Técnicas de Cultura de Células/instrumentação , Proliferação de Células , Sobrevivência Celular , Eletroporação/instrumentação , Desenho de Equipamento , Feminino , Glicosaminoglicanos/química , Humanos , Ácido Hialurônico/química , Células MCF-7 , Proteoglicanas/química
20.
Pathologica ; 110(2): 92-95, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30546144

RESUMO

Intestinal-type adenocarcinoma is a rare primary vaginal carcinoma and considerably more uncommon than metastatic lesions which represent the most frequent malignancy at this anatomic site. Among all malignant tumors, colorectal, breast and female genital tract carcinomas have the tendency to metastasize to the vagina.As morphologic and immunohistochemical features of intestinal-type adenocarcinoma occurring primarily in the vagina are not specific, clinical and radiologic information is crucial to exclude a metastatic lesion.Herein we present a rare case of intestinal-type adenocarcinoma from a villous adenoma, presenting as a polypoid mass in the posterior wall of vaginal introitus of 51-year-old menopausal woman. To the best of our knowledge, only 19 cases of intestinal-type adenocarcinoma of the vagina have been reported in the English literature so far. Notably the origin from a previous villous adenoma has been well documented only in a few cases.


Assuntos
Adenocarcinoma/patologia , Adenoma Viloso/patologia , Neoplasias Vaginais/patologia , Adenocarcinoma/química , Adenocarcinoma/cirurgia , Adenoma Viloso/química , Adenoma Viloso/cirurgia , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Vaginais/química , Neoplasias Vaginais/cirurgia
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